PREMATURE CHROMATIN CONDENSATION UPON ACCUMULATION OF NIMA

The NIMA protein kinase of Aspergillus nidulans is required for the G( 2)/M transition of the cell cycle. Mutants lacking NIMA arrest without morphological characteristics of mitosis, but they do contain an acti vated p37(nimX) kinase (the Aspergillus homologue of p34(cdc2)). To ga in a better understanding of NIMA function we have investigated the ef fects of expressing various NIMA constructs in Aspergillus, fission ye ast and human cells. Our experiments have shown that the instability o f the NIMA protein requires sequences in the non-catalytic C-terminus of the protein. Removal of this domain results in a stable protein tha t, once accumulated, promotes a lethal premature condensation of chrom atin without any other aspects of mitosis. Similar effects were also o bserved in fission yeast and human cells accumulating Aspergillus NIMA . This phenotype is independent of cell cycle progression and does not require p34(cdc2) kinase activity. As gain of NIMA function by accumu lation results in premature chromatin condensation, and loss of NIMA f unction results in an inability to enter mitosis, we propose that NIMA functions in G(2) to promote the condensation of chromatin normally a ssociated with entry into mitosis.